Methods for Protecting a Parathyroid

ABSTRACT

A method includes covering or contacting a portion of a parathyroid of a subject with a shield including extraembryonic tissue and/or a stem cell. The covering or contacting occurs during a neck or reconstructive surgery of the subject.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/425,578, filed May 29, 2019 and incorporated herein by reference inits entirety, which is a continuation-in part of U.S. patent applicationSer. No. 16/219,038, filed Dec. 13, 2018 and now U.S. Pat. No.10,342,631, which is incorporated herein by reference in its entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable.

APPENDIX

Not Applicable.

BACKGROUND

During neck surgeries, such as surgeries on the thyroid, parathyroid,esophagus, trachea, larynx, pharynx, cervical spine, cervical lymphnodes, and carotid arteries, the recurrent laryngeal nerve is subject todamage. For example, the recurrent laryngeal nerve may be damaged as aresult of trauma, desiccation, or the like. As the recurrent laryngealnerve is typically exposed early in operations and is often the mostsuperficial structure in the operative field, it is at risk for injuryduring the remainder of the operation and then during the healing phasewhere it remains the most superficial structure at the healinginterface. Once exposed, the nerve is subject to damage from direct andindirect insults which occur during the natural course of operating anddissecting the adjacent tissues from touching, traction, stretching,friction, desiccation and even inadvertent trauma from surgicalinstruments. As the operative field is kept dry using suction devices orthe like, the nerve is subject to damage from desiccation or thephysical act of keeping the operative field dry using absorbent spongesand the use of suction apparatus. Once exposed it is also highly subjectto injury from thermal or electric injury from cautery devices used innearby tissues. Such damage adversely affects patients as the recurrentlaryngeal nerve is required for phonation and speech. Patients who incurdamage to the recurrent laryngeal nerve may lose their voice for aminimum of 10-12 weeks and approximately 8-10% of patients may have apermanent injury that does not improve. Patients with an injuredrecurrent laryngeal nerve cannot talk normally. They can speak only in awhisper. Patients with an injured recurrent laryngeal nerve alsofrequently aspirate liquids as they cannot adequately protect theirtrachea from food/liquids entering their trachea.

Injury to the recurrent laryngeal nerve is known to occur in asignificant percentage of head and neck operations. To mitigate orreduce the chance of injury to the recurrent laryngeal nerve, manymaneuvers are undertaken by surgeons, but to date, there has been nodecrease to this risk.

During total thyroidectomy the four parathyroid glands are necessarilydissected and disturbed as the parathyroid glands are typicallyimmediately adjacent or attached to the thyroid gland itself. It isexpected that at least one, and often multiple parathyroid glands becomeischemic as their blood supply is disturbed. The incidence ofhypoparathyroidism (lack of parathyroid function) following totalthyroidectomy is between 20 and 75%, depending on the willingness of thesurgeon to measure the parathyroid function in the postoperative period.Clinically significant hypoparathyroidism requiring extendedhospitalization and prolonged treatment with high levels of calciumsupplementation is expected to occur in 12 to 20% of all totalthyroidectomies. In a large retrospective study published in 2018,transient hypoparathyroidism occurred in 68% of patients and permanenthypoparathyroidism occurred in 18% (Teshima M, et al., Auris NasusLarynx. 2018 December; 45(6):1233-1238. doi: 10.1016/j.anl.2018.04.008).Transient hypoparathyroidism is a very significant complication whilepermanent hypoparathyroidism can be life changing and debilitating(Caglia P, et al. Ann Ital Chir. 2017; 6:371-381; Orloff L A, et al.Thyroid. 2018 July; 28(7):830-841. doi: 10.1089/thy.2017.0309).Similarly, during a parathyroid exploration, the parathyroid glands arenecessarily dissected and disturbed as the surgeon searches for eachgland and then determines which of the four glands are enlarged. Thevery act of searching for and then dissecting out each parathyroid glandcan make a normal, small parathyroid gland ischemic in the same way thatidentifying them during thyroid surgery will do. The incidence of one ormore ischemic parathyroid glands following parathyroid surgery isbetween 20 and 80% depending on how extensive the operation is and howdetermined the surgeon is to find all four parathyroid glands.

Hypoparathyroidism is the most common complication following thyroidsurgery and parathyroid surgery (e.g., following thyroidectomy or duringparathyroid surgery) is the most common complication following thyroidsurgery and results in a dramatic increase in patient morbidity and theoverall cost of the procedures. As such, many maneuvers have beensuggested to assure the best possible chance for damaged parathyroidglands to regain their function once they have been injured. Damagedparathyroid glands are very easy to recognize as they become dark red,purple and even near black even though their attachments to theirsurrounding tissues remain intact. Often the glands are not dead, butseverely ischemic for a period of time (weeks or months) and thus mayeventually regain function. Typically, and most commonly, surgeons willcompletely remove a parathyroid gland that appears ischemic so he/shecan “auto-transplant” the gland. This is typically done by removing thegland from the neck, cutting it into multiple very small pieces and theninserting them into a pocket developed in a muscle. Unfortunately, thismaneuver guarantees this gland is non-functioning for at least 2-3months and possibly dooming it to death and non-function forever. Infact, one of the main predictors of hypoparathyroidism is autotransplantof one or more parathyroid glands by the surgeon (Su A, et al. Medicine(Baltimore). 2017 September; 96(39):e8162.doi:10.1097/MD.0000000000008162).

Improved procedures and materials for protecting parathyroid glands areprovided herein that can result in a significant decrease in the lengthof time for patients to return to normal parathyroid function.

SUMMARY

An aspect of the disclosure is a method comprising covering a portion ofa recurrent laryngeal nerve of a subject with a shield comprisingextraembryonic tissue. The covering occurs during a neck surgery of thesubject.

Another aspect of the disclosure is a method comprising exposing arecurrent laryngeal nerve of a subject during a neck surgery of thesubject, and covering a portion of the exposed recurrent laryngeal nervewith a shield comprising amniotic tissue.

Still another aspect of the disclosure is a shield for protecting arecurrent laryngeal nerve of a subject during a surgical procedure. Theshield comprises a layer of extraembryonic tissue having a first endedge, a second end edge, a first end margin adjacent the first end edge,a second end margin adjacent the second end edge, an intermediate regionbetween the first and second end margins, a first curved side edgeextending between the first and second end edges, and a second curvedside edge extending between the first and second end edges. The shielddiverges away from the first end edge and toward the second end edge.

Still another aspect of the disclosure is a method comprising covering aportion of a recurrent laryngeal nerve of a subject with a shieldcomprising biologic tissue, wherein the neck surgery comprisesperforming a procedure on the subject after covering the portion of therecurrent laryngeal nerve with the shield. The procedure comprisesperforming surgery on one or more of a thyroid, parathyroid, esophagus,trachea, larynx, pharynx, cervical spine, cervical lymph node, orcarotid artery.

In another aspect of the disclosure is a method comprising performing aneck surgery on a subject; during the neck surgery, performing aprocedure on a thyroid, parathyroid, or both the thyroid and parathyroidof the subject; during the neck surgery, covering a parathyroid gland ofthe subject with extraembryonic tissue. In certain embodiments, themethods further comprise contacting the parathyroid gland with a stemcell, a stem cell exudate, or a combination thereof.

Still another aspect of the disclosure is a method comprising exposing aparathyroid gland of a subject, and contacting the exposed parathyroidgland with extraembryonic tissue. In certain embodiments, the methodsfurther comprise contacting the parathyroid gland with a stem cell, astem cell exudate, or a combination thereof.

Still another aspect of the disclosure is a method comprising exposing aparathyroid gland of a subject; contacting the parathyroid gland with astem cell, a stem cell exudate, or a combination thereof.

These are merely some of the innumerable aspects of the presentdisclosure and should not be deemed an all-inclusive listing of theinnumerable aspects associated with the present disclosure. These andother aspects will become apparent to those skilled in the art in lightof the following disclosure and accompanying drawings. The descriptionand specific examples in this summary are intended for purposes ofillustration only and are not intended to limit the scope of the presentdisclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and form a part ofthe specification, illustrate the embodiments of the present disclosureand together with the description, serve to explain the principles ofthe disclosure.

FIG. 1 illustrates a schematic top down view of one embodiment of ashield for a recurrent laryngeal nerve.

FIG. 2 illustrates a schematic top down view of an alternativeembodiment of a shield for a recurrent laryngeal nerve.

FIG. 3 illustrates a schematic view of a thyroid and exposed recurrentlaryngeal nerve.

FIG. 4 illustrates a schematic view of the shield of FIG. 1 as appliedto the recurrent laryngeal nerve of FIG. 3.

Reference characters in the written specification indicate correspondingitems shown throughout the drawing figures.

DETAILED DESCRIPTION

Referring to FIGS. 1, 3, and 4, a shield 20 for protecting a recurrentlaryngeal nerve 22 is shown according to one embodiment. The shield 20is shaped to correspond to the shape and structure of the recurrentlaryngeal nerve 22 (e.g., adjacent the thyroid 23). The shape of theshield 20 accommodates the branching of the recurrent laryngeal nerve 22into an external branch 24 and an internal branch 26. The shape of theshield 20 permits the recurrent laryngeal nerve 22 to maintain itsnormal, pre-surgical shape while being protected by the shield 20. Thisshape of the shield 20 negates the need to straighten or otherwisemanipulate the recurrent laryngeal nerve 22 to cover it with the shield.This is advantageous because manipulating the recurrent laryngeal nerve22 may damage the nerve and/or cause scarring. The shaped nature of theshield 20 may provide a further advantage in that the shield need not beshaped to fit the recurrent laryngeal nerve 22. For example, the shield20 may be of a material that is fragile and susceptible to tearing,bunching, or the like. A rectangular, square, or other such shape thatis not tailored to the recurrent laryngeal nerve may bunch up duringapplication over the recurrent laryngeal nerve complicating positioning.The shield may bunch up and adhere to itself such that the shield cannotcover the recurrent laryngeal nerve.

In some embodiments, a parathyroid gland can be covered or contactedwith a shield comprising amniotic tissue. A shield comprised of amniotictissue that is configured to cover or contact a parathyroid gland can bein the form of a square, rectangle, a circle, oblong, or irregularshape. In general, such squares, rectangles, circles, oblongs, orirregular shapes can be at least about 1 centimeter (cm) square, atleast about 1 centimeter in width (for a rectangle or oblong), or about1 centimeter in diameter (for a circle). Examples of shields that can beused to cover or contact a parathyroid gland include but are not limitedto squares of from 0.5 cm×0.5 cm to 2 cm×2 cm, or rectangles or oblongsof from 0.5 cm to 2 cm×0.5 cm to 2 cm, or circles having diameters offrom about 0.5 cm to 2 cm.

In some embodiments, the shield 20 or parathyroid gland shield comprisesextraembryonic tissue. For example, the shield 20 or parathyroid glandshield may be entirely or partially of human amniotic tissue. The shield20 or parathyroid gland shield may be of commercially available amniotictissue such as Surgraft® Dehydrated Amniotic Sheet, BIOVANCE® HumanAmniotic Membrane Allograft, AMNIOEXCEL® Amniotic Allograft Membrane,Biotissue® AmnioGraft®, AMNIOX® amniotic membrane products, or Wright™ACTISHIELD™. In alternative embodiments, the shield is of one or more ofhuman amniotic tissue, human chorionic tissue, animal amniotic tissue,or animal chorionic tissue. For example, the shield 20 or parathyroidgland shield may comprise a combination of human amniotic tissue andhuman chorionic tissue.

In still further alternative embodiments, the shield 20 is of biologictissue suitable for protecting the recurrent laryngeal nerve 22 or theparathyroid gland shield is suitable for protecting a parathyroid gland.The biologic tissue may have one or more of the followingcharacteristics: (1) man-made biologic; (2) surface roughness (e.g.,mean roughness Ra or root mean square roughness RMS) of not more than200% greater than that of suitable human amniotic tissue, and morepreferably of not more than 50% greater than that of suitable humanamniotic tissue, and even more preferably of not more than 25% greaterthan that of suitable human amniotic tissue (where suitable humanamniotic tissue constitutes any of the following commercially availableproducts: Surgraft® Dehydrated Amniotic Sheet, BIOVANCE® Human AmnioticMembrane Allograft, AMNIOEXCEL® Amniotic Allograft Membrane, Biotissue®AmnioGraft®, AMNIOX® amniotic membrane products, and Wright™ACTISHIELD™); (3) dissolvable or absorbable within a few days; (4) thin(e.g., have a thickness such that the tissue is translucent ortransparent); (5) malleable; (6) transparent; (7) translucent; (8)non-inflammatory; (9) non-immunogenic such that it poses little if anyrisk of foreign body reaction; and (10) flexible such that the tissuetakes on the shape of surrounding tissue (e.g., the tissue retains thegeneral curved shape but is sufficiently flexible to conform to thetissues on which the tissue lays). In still further embodiments, theshield 20 or parathyroid gland shield comprises a combination ofbiologic tissue and other tissue (e.g., human amniotic tissue, humanchorionic tissue, animal amniotic tissue, and/or animal chorionictissue).

The shield 20 may comprise compounds and/or materials to assist inprotection of the recurrent laryngeal nerve 22 and/or assist in healingof the recurrent laryngeal nerve and/or surrounding tissues followingthe procedure. Similarly, the parathyroid gland shield may comprisecompounds and/or materials to assist in protection of the parathyroidgland and/or assist in healing of the parathyroid gland and/orsurrounding tissues following the procedure. For example, and withoutlimitation, the shield may comprise an extracellular Matrix (ECM),growth factors, fibronectin, proteoglycans, laminin, and/or otherproteins. The shield 20 or parathyroid gland shield may downregulateTGF-B, inhibit MMP's, suppress inflammatory cytokines, promoteangiogenesis, suppress cell death (e.g., parathyroid gland cell death),and/or decrease fibroblast formation.

Regardless of material, the shield 20 or parathyroid gland shield istypically cut from a sheet of the material before it is provided to asurgeon. This allows a surgeon to use the shield 20 or parathyroid glandshield without cutting out the shield from a sheet which takes time andcan be difficult to do without damaging the material. The shield 20 orparathyroid gland shield may be cut from a sheet of material during amanufacturing process using a die cutting system or the like. Thisprovides for more accurate shaping and a reduction in damage to theshield material in comparison to other techniques such as using scissorsor a scalpel to cut the shape of the shield. Typically, the sheet willbe of a relatively uniform thickness resulting in a shield 20 orparathyroid gland shield having a relatively uniform thickness. Forexample, and without limitation, the thickness of the shield 20 orparathyroid gland shield does not deviate at any one point more than 20%from the average thickness of the shield.

The shield 20 protects the recurrent laryngeal nerve 22 from rubbingand/or friction. The shield 20 further protects the recurrent laryngealnerve 22 from desiccation by covering the nerve. The shield 20 furtherprotects the recurrent laryngeal nerve 22 from electrical injury frominstruments by providing an insulating layer and/or alternativeelectrical path. The shield 20 still further protects the recurrentlaryngeal nerve 22 from bacteria or other pathogens by serving as abarrier when applied. When constructed of amnion, the shield 20 mayfurther have anti-bacterial properties in addition to forming a barrier.

As shown in FIGS. 1 and 4, the shape of the shield 20 includes severalfeatures to accommodate the recurrent laryngeal nerve 22 to provide atleast the benefits described herein (e.g., being shaped to match therecurrent laryngeal nerve 22 such that the shield's dimensions need notbe modified before being applied to the recurrent laryngeal nerve 22).The shield 20 includes a first end edge 28 and a second end edge 30opposite the first end edge 28. The shield 20 diverges away from thefirst end edge 28 and toward the second end edge 30. A first curved sideedge 32 extends between the first 28 and second 30 end edges, and asecond curved side edge 34 extends between the first 28 and second 30end edges. Resulting from the divergence, the shield 20 includes anarrow region 36 and a flared region 38. The narrow region 36 isnarrower than the flared region 38. The second end edge 30 of the flaredregion extends adjacent the larynx 40 of the subject when the shield isapplied to the recurrent laryngeal nerve 22. The external 24 andinternal 26 branches of the recurrent laryngeal nerve 22 enter thelarynx 40, and the second end edge 30 and the shield 20 are shaped suchthat the second end edge 30 is adjacent the larynx 24 and the flaredregion 38 covers the branching of the recurrent laryngeal nerve 22. Thecurvature of each of the first and second curved side edges 32, 34follows the curvature of the upper aspect 42 of the recurrent laryngealnerve 22.

The shield 20 has a length L of between 3.5 centimeters and 4.5centimeters, inclusive. In some embodiments, the length L isapproximately 4 centimeters. In some embodiments, the shield 20 has amaximum width W of between 0.5 centimeters and 1.5 centimeters,inclusive. In some embodiments, the maximum width W is approximately 1centimeter. The shield 20 is sized to overlay and cover the recurrentlaryngeal nerve 22. In some embodiments, the shield 20 is sized suchthat the shield 20 overlays either side of recurrent laryngeal nerve 22by approximately 2-4 millimeters. The overlay allows the shield 20 toadhere to the underlying tissues as a result of water surface tensionand to move with the recurrent laryngeal nerve 22 rather than moveacross or separately from the underlying tissues.

It should be noted that ideally the shield 20 is reversible such thatthe shield 20 may be applied to either a right or a left recurrentlaryngeal nerve 22. The shield 20 may be flipped over as needed to alignwith either nerve. Alternatively, the shield 20 may be available in aright or left version.

Referring now to FIG. 2, an alternative embodiment of a shield 120 isshown. The shield 120 is similar to or the same as the shield 20discussed with reference to FIG. 1 with like part numbers referring tolike features (e.g., the first end edge 28 is the same as the first endedge 128). The shield 120 includes a second end edge 130 that extendsalong a 30 degree angle A that corresponds to the typical angle of therecurrent laryngeal nerve 22 as it enters the larynx 40.

Referring to FIG. 4, the shield 20 or 120 is used in covering a portionof the recurrent laryngeal nerve 22 of a subject. Advantageously, theshield 20 is provided pre-cut to the surgeon for use in protecting therecurrent laryngeal nerve such that the handling of the shield isreduced. In some embodiments, the shield 20 is provided to a surgeon asa part of a kit for use with a procedure of the type described herein.In one embodiment, the kit includes the shield 20 for covering therecurrent laryngeal nerve and a cotton tip swab for applying the shield.The cotton tip swab be treated or otherwise pre-prepared to be adaptedfor use with the shield. For example, the cotton tip swab may be asterilized cotton tip swab.

The covering of the recurrent laryngeal nerve occurs during a necksurgery. The neck surgery comprises performing a procedure on thesubject after covering the portion of the recurrent laryngeal nerve withthe shield. The procedure comprises performing surgery on one or more ofa thyroid, parathyroid, esophagus, trachea, larynx, pharynx, cervicalspine, cervical lymph node, or carotid artery. For example, during athyroidectomy, the recurrent laryngeal nerve 22 is exposed. The shield20 will typically be applied promptly after exposure of the recurrentlaryngeal nerve 22. This protects the recurrent laryngeal nerve 22during the remainder of the thyroidectomy and the completion of the necksurgery. In this example, the remainder of the thyroidectomy constitutesthe procedure. In some cases, the procedure may be prolonged, e.g., by aneck dissection to remove local lymph nodes. In such cases, the shield20 protects the recurrent laryngeal nerve 22 throughout (e.g., preventsdesiccation and decreases the likeliness of electrical injury or directinstrument trauma during a prolonged procedure). The surgeon refrainsfrom removing the shield 20 from the recurrent laryngeal nerve 22 duringthe neck surgery and the shield 20 is left in the subject post-surgery.

During the procedure, such as the remainder of the thyroidectomy or anyof the other procedures, the surgeon refrains from moving the shield 20relative to the recurrent laryngeal nerve 22. When placing the shield 20over the recurrent laryngeal nerve 22, the flared region 38 overlays theexternal and internal branches 24, 26 of the recurrent laryngeal nerve22. The narrow region 36 covers a portion of the recurrent laryngealnerve 22 prior to the branching. The second end edge 30 of the shield 20extends adjacent the larynx 40. The recurrent laryngeal nerve 22 is inits pre-surgical shape upon being covered. In other words, the recurrentlaryngeal nerve 22 is not reshaped (e.g., straightened) before beingcovered by the shield 20. The shape of the shield 20 also facilitatesthe placement of the shield 20 while avoiding creases or folds in theshield 20. Further, when placing the shield 20 over the recurrentlaryngeal nerve 22, the first curved side 32 and the second curved side34 follows the curvature of the curved upper aspect of the recurrentlaryngeal nerve 22.

In an example of placing the shield 20, a first end margin 44 of theshield 20 is grasped and a second end margin 46 of the shield 20 isgrasped. The shield 20 is oriented relative to the recurrent laryngealnerve 22 such that the second end edge 30 of the shield 20 is adjacentthe larynx 40 of the subject and such that the curvature of each of thefirst 32 and second 34 side edges corresponds to the curvature of thecurved upper aspect of the recurrent laryngeal nerve 22. The shield 20is brought into contact with the recurrent laryngeal nerve 22 such thata portion of the shield 20 contacts the nerve 22 while the grasping ofat least one of the two end margins is maintained. For example, acotton-tip swab is used to press an intermediate portion of the shield20 to the recurrent laryngeal nerve 22. Next, the grasp on at least oneof the two end margins is released. For example, the shield 20 isapplied from the intermediate portion outward toward the two oppositeends.

After the recurrent laryngeal nerve 22 is covered, at least partially,by the shield 20, surgery procedure is performed (e.g., the removal ofthe thyroid in a thyroidectomy) by the surgeon. This allows the shield20 to protect the recurrent laryngeal nerve 20 throughout the procedureand during any other portion of the operation (e.g., such as a neckdissection for lymph node removal) and/or after the procedure iscompleted. As such, the shield 20 reduces the chances of damage to therecurrent laryngeal nerve 22 and/or other negative outcomes of the typedescribed herein.

In some embodiments, the shield 20 is left in place at the conclusion ofthe operation to protect the exposed surface of the recurrent laryngealnerve from the movement of muscles and other tissues which lay acrossthe exposed surface of the recurrent laryngeal nerve which is subject totrauma from friction during movement of the neck during the healingprocess. The shield 20 may also prevent scar formation between therecurrent laryngeal nerve and overlying tissues which ordinarily wouldnot be adjacent to the recurrent laryngeal nerve. At the conclusion ofthe operation, the recurrent laryngeal nerve is exposed and laying uponthe top surface of underlying tissues. When the wound is closed, thetissues above are laid down on the recurrent laryngeal nerve and thusthe recurrent laryngeal nerve is exposed within the interface of the twotissue bodies. In such a situation, movement of the patient's neck (evenminor movement) causes the recurrent laryngeal nerve to be rubbed on andtraumatized by the overlying muscles and tissues. This can causeinjuries to the recurrent laryngeal nerve during the first 24 hoursafter the procedure until the tissues begin to stick together and nolonger slide relative to each other at the interface between theunderlying and overlying tissues. The shield 20 minimizes or preventssuch rubbing and may reduce or prevent such injuries.

Although discussed with respect to certain exemplary operations herein,the shield 20 is suitable for use during any operation in which therecurrent laryngeal nerve is exposed. For example, other procedures mayinclude anterior cervical spine fusion, Carotid endarterectomy, centralneck dissection for lymph nodes and or cancers of various types,cricopharyngeal myotomy, esophagectomy (cervical approach), excision ofZenker's diverticulum, hemithyroidectomy or other partial thyroidectomy,lateral neck dissection for lymph nodes and/or cancer of various types,modified radical neck dissection (or radical neck dissection), neckbiopsy, parathyroidectomy of all forms, partial laryngectomy, substernalgoiter resection, and thyroidectomy partial or total.

Also provided herein are methods for covering or contacting aparathyroid gland with a parathyroid gland protective injection. Suchparathyroid gland protective injections can comprise liquids or flowableliquids that can be delivered to the parathyroid gland and/or adjacentregions with a syringe or other device. Parathyroid gland protectiveinjections provided herein can be used either alone or in conjunctionwith a parathyroid shield.

In some embodiments, the parathyroid gland protective injections cancomprise delivery of injectable liquid or flowable forms of amniotictissue around and/or on a parathyroid gland. Suitable forms ofinjectable amniotic tissue include liquid or flowable forms ofextraembryonic tissue (e.g. one or more of human amniotic tissue, humanchorionic tissue, non-human amniotic tissue, or non-human chorionictissue). Suitable forms of injectable amniotic tissue include but arenot limited to flowable amniotic membrane allografts that are typicallyinjected into joints are available in in 0.5 cc, 1 cc, and 2 cc vialsfrom various manufacturers (e.g. SurForce®, Surgenex, Scottsdale, Ariz.,85260) and can be adapted for use in the methods for protectingparathyroid glands provided herein.

In some embodiments, the parathyroid gland protective injections cancomprise delivery of stem cell, a stem cell exudate, or a combinationthereof around and/or on a parathyroid gland. In some embodiments, thestem cell and/or stem cell exudate is an autologous stem cell and/or anautologous stem cell exudate. In some embodiments, the stem cell and/orstem cell exudate is an allogeneic stem cell and/or an allogeneic stemcell exudate. Non-limiting examples of autologous or allogenic stemcells and stem cell exudates include bone marrow, molar, peripheralblood, adipose, amniotic fluid, and umbilical cord blood stem cells andstem cell exudates. Stem cell exudates that can be used include stemcell conditioned media and components thereof. Stem cell conditionedmedia can be obtained by culturing the stem cells in media from about 16hours to about five days (Pawitan J A. 2014; 2014:965849. doi:10.1155/2014/965849). In certain embodiments, the stem cell exudatecomprises one or more growth factors, cytokines, and/oranti-inflammatory agents. Such growth factors include but are notlimited to VEGF, FGF2, EGF, HGF, PIGF, SDF-1, PDGF, TGF-beta1, and PDEGF(Ibid). Such cytokines include but are not limited to IL-8, IL-9, UPA,thrombospondins 1 and 2, serpin E-1, SDF-1, TIMP-1, IGFBP, ADM, and DKK1 (Ibid). Antiinflammatory agents include but are not limited to IL-10,IL-1ra, IL-13 and IL-27 (Zagoura et al. Gut. 2012 June; 61(6):894-906.doi:10.1136/gutjnl-2011-300908).

The covering or contacting of the parathyroid gland can occur during aneck surgery (e.g., following a thyroidectomy or during or following aparathyroid surgery) or in reconstructive surgery (e.g., following aninjury to the neck). The neck surgery procedures where the parathyroidgland can be covered or contacted as disclosed herein can compriseperforming surgery on one or more of a thyroid, parathyroid, esophagus,trachea, larynx, pharynx, cervical spine, cervical lymph node, orcarotid artery. For example, during a thyroidectomy and duringparathyroid surgery, the parathyroid glands exposed and/or perturbed.The parathyroid shield and/or parathyroid gland protective injection canbe applied at any stage during the procedure but is most typicallyperformed once actions that will expose and/or perturb the parathyroidgland are complete (e.g., after a thyroidectomy or after commencement ofthe procedure on the thyroid). In some embodiments, the parathyroid iscovered or contacted by a step comprises laying the layer ofextraembryonic tissue over the parathyroid gland. In some embodiments,the covering or contacting of the parathyroid glands comprises injectingparathyroid gland protective injection (e.g., with extraembryonictissue, stem cells, stem cell exudates, and/or any combination thereof)on and/or adjacent the parathyroid gland. In some embodiments, theparathyroid gland that is covered or contacted is ischemic orpre-ischemic. In some embodiments, the parathyroid gland(s) are removedand autotransplanted to another location and covered or contacted andthe shield or injected material is left in the subject post-surgery. Insome embodiments, the parathyroid gland is left in situ (e.g. is nottransplanted) during the surgery and covered or contacted with theparathyroid shield and/or parathyroid gland protective injection. Insome embodiments, the surgeon refrains from removing the parathyroidgland shield or parathyroid gland protective injection from theparathyroid gland during the neck or reconstructive surgery and theshield or injected material is left in the subject post-surgery. Incertain embodiments, the subject's parathyroid function as measured byparathyroid hormone (PTH) levels and serum calcium levels is monitoredbefore surgery to establish a baseline PTH and calcium levels and/or atvarious intervals post-surgery (e.g., at about 1, 2, 3, or more monthspost-surgery). It is anticipated that subjects receiving a parathyroidshield and/or a parathyroid gland protective injection will return tobaseline or near baseline levels of parathyroid function (e.g., at leastabout 50%, 75%, or 90% of baseline PTH and calcium levels) more quickly(e.g., within about 1, 2, 3, or more months post-surgery) in comparisonto control cohort subjects who have undergone similar procedures buthave not received a parathyroid shield and/or a parathyroid glandprotective injection.

In view of the foregoing, it will be seen that the several advantages ofthe disclosure are achieved and attained.

The embodiments were chosen and described in order to best explain theprinciples of the disclosure and its practical application to therebyenable others skilled in the art to best utilize the disclosure invarious embodiments and with various modifications as are suited to theparticular use contemplated.

As various modifications could be made in the constructions and methodsherein described and illustrated without departing from the scope of thedisclosure, it is intended that all matter contained in the foregoingdescription or shown in the accompanying drawings shall be interpretedas illustrative rather than limiting. Thus, the breadth and scope of thepresent disclosure should not be limited by any of the above-describedexemplary embodiments, but should be defined only in accordance with thefollowing claims appended hereto and their equivalents.

What is claimed is:
 1. A method comprising: performing a neck surgery ona subject; during the neck surgery, performing a thyroid procedure or aparathyroid procedure on the subject; during the neck surgery, coveringa parathyroid gland of the subject with extraembryonic tissue, whereinthe parathyroid gland is ischemic during the covering of the parathyroidgland with extraembryonic tissue.
 2. The method as set forth in claim 1wherein the performing comprises performing a thyroidectomy.
 3. Themethod as set forth in claim 2 wherein the covering of the parathyroidgland with the extraembryonic tissue occurs after the thyroidectomy. 4.The method as set forth in claim 1 wherein the contacting of theparathyroid gland with the extraembryonic tissue occurs aftercommencement of the thyroid procedure or the parathyroid procedure. 5.The method as set forth in claim 1 further comprising refraining fromremoving the extraembryonic tissue from the subject during the necksurgery such that the extraembryonic tissue is in the subjectpost-surgery.
 6. The method as set forth in claim 1 wherein theextraembryonic tissue comprises a layer of extraembryonic tissue, andwherein the covering step comprises laying the layer of extraembryonictissue over the parathyroid gland.
 7. The method as set forth in claim 1wherein the covering of the parathyroid gland with the extraembryonictissue comprises injecting the extraembryonic tissue on and/or adjacentthe parathyroid gland.
 8. The method as set forth in claim 1 wherein theparathyroid gland is in-situ during the covering of the parathyroidgland with the extraembryonic tissue.
 9. The method as set forth inclaim 1, wherein the performing comprises performing the parathyroidprocedure, and wherein the parathyroid procedure comprises removing theparathyroid gland from its original location and auto-transplanting theparathyroid gland.
 10. The method as set forth in claim 1 wherein theextraembryonic tissue comprises one or more of human amniotic tissue,human chorionic tissue, non-human amniotic tissue, or non-humanchorionic tissue.
 11. The method as set forth in claim 1 wherein theextraembryonic tissue comprises amniotic tissue and chorionic tissue.12. The method as set forth in claim 1 further comprising contacting theparathyroid gland with a stem cell, a stem cell exudate, or acombination thereof.
 13. The method as set forth in claim 11 wherein thestem cell and/or stem cell exudate is an autologous stem cell and/or anautologous stem cell exudate.
 14. A method comprising: performing a necksurgery on a subject; during the neck surgery, performing a thyroidprocedure or a parathyroid procedure on the subject; during the necksurgery, contacting a parathyroid gland of the subject withextraembryonic tissue, wherein the parathyroid gland is ischemic duringthe contacting of the parathyroid gland with extraembryonic tissue. 15.The method as set forth in claim 14 wherein the extraembryonic tissuecomprises a layer of extraembryonic tissue, and wherein the contactingof the parathyroid gland with the extraembryonic tissue comprises layingthe layer of extraembryonic tissue over the parathyroid gland.
 16. Themethod as set forth in claim 14 wherein the contacting of theparathyroid gland with the extraembryonic tissue comprises injecting theextraembryonic tissue adjacent the parathyroid gland.
 17. The method asset forth in claim 16 wherein the extraembryonic tissue is a liquidduring the contacting of the parathyroid gland with the extraembryonictissue.
 18. The method as set forth in claim 14 wherein the parathyroidgland is in-situ during the contacting step.
 19. The method as set forthin claim 14, further comprising removing the parathyroid gland from itsoriginal location and auto-transplanting the parathyroid gland.
 20. Themethod as set forth in claim 14 wherein the extraembryonic tissuecomprises one or more of human amniotic tissue, human chorionic tissue,non-human amniotic tissue, or non-human chorionic tissue.
 21. The methodas set forth in claim 14 wherein the extraembryonic tissue comprisesamniotic tissue and chorionic tissue.
 22. The method as set forth inclaim 21 wherein the parathyroid gland is in-situ during the contactingstep.
 23. The method as set forth in claim 14 further comprisingcontacting the parathyroid gland with a stem cell, a stem cell exudate,or a combination thereof.
 24. The method as set forth in claim 23wherein the stem cell and/or stem cell exudate is an autologous stemcell and/or an autologous stem cell exudate.
 25. A method comprising:performing a neck surgery on a subject; during the neck surgery,performing a thyroid procedure or a parathyroid procedure on thesubject; during the neck surgery, contacting a parathyroid gland of thesubject with a stem cell, wherein the parathyroid gland is in-situduring the contacting of the parathyroid gland with the stem cell. 26.The method as set forth in claim 25 wherein the parathyroid gland isischemic during the contacting of the parathyroid gland with the stemcell.
 27. The method as set forth in claim 26 wherein the stem cell isan autologous stem cell.
 28. The method as set forth in claim 26 whereinthe stem cell is an adipose, molar, peripheral blood, amniotic fluid,umbilical cord blood, or bone marrow stem cell.
 29. The method as setforth in claim 25 further comprising refraining from removing the stemcell from the subject during the neck surgery such that the stem cell isin the subject post-surgery.
 30. The method as set forth in claim 25wherein the subject's parathyroid hormone (PTH) and serum calcium levelsare monitored before contacting the parathyroid gland of the subjectwith the stem cell and/or at various intervals after contacting theparathyroid gland with the stem cell and wherein the subject's PTH andserum calcium levels return to baseline or near baseline levels morequickly in comparison to control cohort subjects who have undergonethyroid or parathyroid procedures without a stem cell contacting aparathyroid gland.